Anion secretory effects of a non-peptide mimic of bradykinin (FR190997) on mouse colon epithelium

Abstract

FR190997, a new non-peptide mimic was investigated using the chloride secretory response of the mouse colon as a test system. The increase in short circuit current (SCC) to FR190997 was approximately equal to that of lysyl bradykinin (LBK). It is shown that the current increase to FR190997 is due to electrogenic chloride secretion through an action at B2-kinin receptors and involves prostaglandin formation. In these respects its actions are identical to those of LBK, except that the responses to FR190997 are prolonged. However FR190997 produces a long lasting desensitisation both to itself and to LBK and it did not prove possible to protect against this using the high affinity antagonist at B2 receptors, Hoe 140. It is suggested that FR190997 either slows receptor recycling or leads to degradation of receptors, such that the reappearance of sensitivity may depend on new receptor synthesis.